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WO2004083869A1 - Procede d'evaluation de la capacite antioxydante d'un echantillon d'organisme - Google Patents

Procede d'evaluation de la capacite antioxydante d'un echantillon d'organisme Download PDF

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Publication number
WO2004083869A1
WO2004083869A1 PCT/JP2004/003873 JP2004003873W WO2004083869A1 WO 2004083869 A1 WO2004083869 A1 WO 2004083869A1 JP 2004003873 W JP2004003873 W JP 2004003873W WO 2004083869 A1 WO2004083869 A1 WO 2004083869A1
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WIPO (PCT)
Prior art keywords
antioxidant
oxidation
oxidation reaction
biological sample
disease
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Ceased
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PCT/JP2004/003873
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English (en)
Japanese (ja)
Inventor
Osamu Cynshi
Roland Stocker
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Heart Research Institute Ltd
Chugai Pharmaceutical Co Ltd
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Heart Research Institute Ltd
Chugai Pharmaceutical Co Ltd
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Application filed by Heart Research Institute Ltd, Chugai Pharmaceutical Co Ltd filed Critical Heart Research Institute Ltd
Priority to JP2005503775A priority Critical patent/JPWO2004083869A1/ja
Priority to EP04722400A priority patent/EP1612559A4/fr
Priority to US10/549,676 priority patent/US20060177888A1/en
Publication of WO2004083869A1 publication Critical patent/WO2004083869A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors

Definitions

  • the present invention relates to a method for evaluating antioxidant capacity against oxidative stress in a living body.
  • Aerobic organisms including humans, gain energy through oxidative phosphorylation by oxygen.
  • This oxidative phosphorylation proceeds via oxygen radicals generated from oxygen. Therefore, the presence of oxygen radicals is essential for living organisms.
  • oxygen radicals are also considered to be oxidative stress that oxidizes tissues or biological components in the body, and the oxidative stress causes cataracts, diabetes, Alhaima, cancer, arteriosclerosis, cardiopulmonary disease, and hypercholesterolemia.
  • Oxidative stress oxidants and antioxidants. Review. Exp. Physiol. 82: 291-5, which is known to be an exacerbating factor for various diseases such as chronic inflammatory diseases and ischemic diseases. Scott G. (1997) Antioxidants in science, technology, medicine and nutrition. Coll House, UK Publishing; Porter NA (1990) Auto-oxidation of polyunsaturated fatty acids:
  • antioxidant ability has been evaluated by measuring oxidation products that have already been oxidized in vivo, or by taking a biological sample that has not yet been oxidized and causing oxidation ex vivo to oxidize the sample. It is known how to check the difficulty.
  • lipid peroxide which is a TBA-reactive substance, as an oxidation product has been used for a long time (Yagi K. A simple fluorometnc) assay for liDOperoxide in blood plasma. Biochem Med. 1976 15: 212-6.).
  • lipid peroxide produced in vivo is measured by heating the lipid peroxide together with TB A under acidic conditions and measuring the intensity of the generated fluorescence.
  • this method does not provide information on where the lipid peroxide was formed in the living body and what kind of reaction was caused by the method.
  • a sample is taken out of a living body and then subjected to an oxidation reaction outside the body, whereby the sample is contained in the sample.
  • a TAS method using a serum or tissue homogenate sample (Total Antioxidant Status method; Rice-Evans C, Miller NJ. Total antioxidant status in plasma and body fluids. Methods Enzymol. 1994 234: 279-93.) Is used as a clinical test method.
  • the TAS method hydrogen peroxide and metmyoglobin are used as oxidizing agents to initiate an oxidation reaction by a radical reaction via iron ion, and the ability of a sample to resist this oxidation reaction is measured. It evaluates the antioxidant capacity of the sample. Since this method has a short reaction time of typically 6 minutes, it can be measured with an automatic analyzer.
  • TRAP is a method that uses the oxidation reaction of 2,2'-azobis (2-amidinopropane) hydrochloride (AA PH), which can generate radicals constantly.
  • AA PH 2,2'-azobis (2-amidinopropane) hydrochloride
  • the method (Total Radical-trapping Antioxidant Potential) has also been developed (Wayner DD, Burton GW, Ingold KU, Locke S. Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation.The important contribution made by plasma proteins. FEBS Lett. 1985 187: 33-7).
  • the method of inducing oxidation of a biological sample ex vivo can evaluate a specific antioxidant ability in the sample that can react with a radical.
  • lipid peroxidation chain reaction occurs by adding copper ion to an LDL sample ex vivo and keeping it at 37 to evaluate the antioxidant ability of the LDL sample against this lipid peroxidation reaction. are doing.
  • the formation of oxide was evaluated by the absorbance at 234 nm, and the reaction was started. It is thought that the lag time from the start until the change in the absorbance at 2334 nm begins to be detected reflects the amount of antioxidant components in the sample.
  • the oxidation reaction is performed ex vivo until the antioxidant component contained in the sample disappears, and the antioxidant component has the total amount of the antioxidant component. I regard it as an ability.
  • the main antioxidant component in the samples used in these evaluation methods is considered to be the most antioxidant molecular species of vitamin E — tocopherol. Oxidizing components Free radicals and biological defense, 1994 Society Press).
  • the total amount of ⁇ -tocopherol is mainly evaluated as the antioxidant ability, so that the higher the content of single tocopherol in a sample from an individual, the higher the individual
  • the antioxidant capacity has been evaluated as being high, that is, the individual is unlikely to suffer from diseases such as arteriosclerosis and ischemic disease that are exacerbated by oxidative stress.
  • kits for performing these methods are commercially available from Randox Laboratories Ltd., OXIS International, Inc. and others as useful for clinical diagnosis.
  • the present invention provides a method for evaluating the antioxidant ability of a living body against oxidation occurring in the presence of an antioxidant component.
  • the present inventors have focused on the existence of an oxidation reaction that proceeds even in the presence of an antioxidant component, and as a result of repeated research, have found a method for measuring such an oxidation product.
  • the present invention provides a method for evaluating the antioxidant capacity of a biological sample, comprising:
  • the present invention is also an invention of a method for diagnosing a disease or evaluating the prognosis of a disease state and predicting Z or progress of a target patient based on the antioxidant ability of a biological sample evaluated by this method.
  • the present invention is a method for evaluating the antioxidant capacity of an antioxidant test component, comprising:
  • step (c) initiating the oxidation reaction of the mixture of step (b);
  • FIG. 1 shows a representative HPLC chart of the treatment solution after the oxidation reaction was stopped in Example 1.
  • the peaks with a retention time of about 9 minutes are CEOOH and CEOH, and the peak with a retention time of about 5 minutes is 0! —Tokofueru. 200
  • FIG. 2 shows a graph showing the relationship between AAPH concentration and oxidation products.
  • the horizontal axis is the AAPH concentration, and the vertical axis is the sum of the production amounts of cholesterol ester hydroperoxide (CEO OH) and cholesterol ester hydroxide (CE OH).
  • C Fig. 3 shows 0; -tocopherol in Example 2.
  • a representative HPLC chart of the oxidation reaction solution in which disappeared is shown.
  • FIG. 4 is a graph showing changes in the amounts of CEOOH and CEO in the presence of various concentrations of ⁇ -tocopherol, probucol or ⁇ -653.
  • One aspect of the present invention is to initiate an ex vivo oxidation reaction in a biological sample containing an antioxidant component and an oxidizable substrate, and to perform the oxidation reaction in a state where the antioxidant component is not consumed by the oxidizing species. And evaluating the antioxidant ability of the biological sample, which comprises quantifying the oxidizable substrate oxidized by the oxidation reaction. In this method, the antioxidant ability of the biological sample, and thus of the individual from which the biological sample has been removed, will be evaluated.
  • the target organism in this method is a mammal, preferably a human.
  • Biological samples include tissue homogenates, lymph, urine, blood, plasma and serum.
  • the tissue from which the sample is removed is not particularly limited, and includes skin, liver, blood vessel walls, blood, and urine, and is preferably blood.
  • the sample used in the method of the present invention is used at the same concentration in the living body or after diluting it up to 1000 times, preferably up to 10 times. Dilution is preferably performed with physiological saline.
  • a chelator may be added to prevent oxidation of the sample. Generally, it is preferable to adjust the value to 3 to 10 to 11.
  • the “antioxidant component” naturally contained in a biological sample in the method of the present invention is a general term for an easily oxidizable substance possessed by a living body to resist oxidative stress, and in particular, ⁇ -tocopherol Can be mentioned.
  • This antioxidant component offsets the oxidizing species in the system by being oxidized before coexisting oxidizable substrates in the sample, thereby preventing the oxidizable substrate from being oxidized. It has been considered to work.
  • one tocopherol may not be a lipid in certain experimental conditions. It has been reported that it promotes peroxidation, so it does not necessarily prevent oxidizable substrates from being oxidized.
  • oxidizable substrate used in the method of the present invention includes, for example, when the sample is blood, plasma or serum, lipids such as cholesterol esters, neutral lipids, and phospholipids; Cholesterol ester is a major oxidizable substrate.
  • the oxidation reaction in the method of the present invention can be initiated by adding an oxidation initiator, by irradiation such as ultraviolet light or radiation, or by auto-oxidation.
  • an oxidation initiator is a preferred method of initiation because it is easy to control the intensity of the oxidation reaction by increasing or decreasing its type or amount.
  • Oxidation initiators used include, for example, peroxides such as hydrogen peroxide and t-butyl hydroperoxide; metal salts such as iron chloride and copper sulfate; 2,2, -azobis (2-amidino).
  • Azo initiators such as propane) hydrochloride (AA PH), 2,2, -azobis (2,4-dimethylvaleronitrile) and 2,2, -azobis (4-methoxy-2,4-dimethylvaleronitrile); copper, Transition metals such as iron and hemin; and hypochlorite, heme iron and hemoglobin.
  • Enzymes may also be used as oxidation initiators, and include, for example, lipoxidase, cyclooxygenase and lactoperoxidase. These oxidation initiators may be used alone or in combination of two or more. It is preferable to use AAPH alone since it can be adjusted to an oxidation reaction of appropriate strength.
  • AAPH is used as the oxidation initiator, and when the biological sample is plasma, the AAPH concentration is 5 to 3 O mM, preferably 5 to 20 mM, more preferably 5 to 20 mM. It is 8 to 12 mM, most preferably 1 O mM.
  • ultraviolet rays or radiation In order to start the oxidation reaction by irradiation, it is preferable to use ultraviolet rays or radiation.
  • Autoxidation can be initiated by exposing the sample to air or oxygen. The temperature at which oxidation is initiated is generally between 20 and 5 Ot, preferably at 37 ° C.
  • the term "in the presence of one or more antioxidant components” as used in the method of the present invention refers to a condition where the antioxidant component has not been consumed by the redox reaction with the oxidizing species. By maintaining such a state, It created a situation in which oxidation, or oxidation promoted by it, that could not be prevented by antioxidant components, which had been thought to block the oxidation of the oxidizable substrate. In some cases, a state in the presence of an antioxidant component may be artificially created by adding an antioxidant to a biological sample.
  • the antioxidant added may be the same or different from the antioxidant naturally contained in the biological sample.
  • the antioxidant naturally contained in the biological sample It is preferably the same substance as above or one of the antioxidant components contained in the biological sample, and more preferably one of the antioxidant components contained in the biological sample.
  • Antioxidants that are different from the antioxidants inherently contained in biological samples include fat-soluble antioxidants such as butylated hydroxytoluene (BHT) and water-soluble antioxidants such as Trolox. included.
  • BHT butylated hydroxytoluene
  • Trolox water-soluble antioxidants
  • the type of oxidation reaction that continues after initiation depends on the means of initiation. Generally, when oxidation is initiated by an oxidation initiator or irradiation, a radical oxidation reaction occurs.
  • the specific conditions of the oxidation reaction may be any conditions under which the oxidation of the oxidizable substrate proceeds and the antioxidant component is present until the oxidation reaction stops. However, specific oxidation reaction conditions can be set by variously changing conditions such as sample concentration, oxidation initiator concentration, temperature and time.
  • the temperature is between 20 and 50 ° C, preferably 37 ° C. Generally, it is carried out at the same temperature as at the start of the oxidation reaction.
  • the time for continuing the oxidation reaction after the start is preferably 2 to 10 hours, more preferably 4 to 8 hours.
  • the biological sample is plasma
  • the oxidation initiator is AAPH and its concentration is 5 to 30 mM, preferably 5 to 20 mM, more preferably 8 to 12 mM. Most preferably, it is 1 O mM
  • the reaction temperature is between 20 and 50 ° C., preferably 37 ° C.
  • the reaction time is within 24 hours, preferably within 8 hours.
  • Oxidation products of oxidizable substrates can be obtained either by measuring the rate of the oxidation reaction or by measuring the amount of components in the oxidation reaction solution after the oxidation reaction has stopped. it can.
  • Methods for measuring the rate of the oxidation reaction include a method of measuring the rate at which the oxidizable substrate is reduced by oxidation, a method of monitoring the progress of oxidation by adding a marker substance and monitoring its fluctuation. Methods for measuring the rate of increase in oxidation products generated by oxidation of oxidizable substrates are included.
  • Specific methods for measuring oxidizable substrates that decrease due to oxidation include, for example, measurement of oxygen consumption, Measurement of the decrease in unsaturated lipids and measurement of the decrease in daltathione.
  • Specific methods of adding a marker substance and monitoring the progress of oxidation by its fluctuation include, for example, a method using a spin and a wrapping agent as a marker substance, a method using a fluorescent substance as a marker substance, and the like. Is raised.
  • the method of measuring the rate of increase of the oxidation product generated by the oxidation of the oxidizable substrate is the same as the method of quantifying the oxidizable substrate in the oxidation reaction solution after the termination of the oxidation reaction described below.
  • the concentration of the oxidized substrate and the concentration of the unoxidized substrate are measured even if the oxidized substrate is quantified. Then, the oxidation rate may be determined from the ratio. In either case, the oxidation reaction is stopped or attenuated by quenching, usually by immersing the container containing the oxidation reaction solution in ice water, or by inhibiting the oxidation by adding a strong antioxidant. Next, the oxidizable substrate and / or the unoxidized oxidizable substrate are separated from the oxidation reaction solution. Separation is performed by methods such as extraction, electrophoresis, and column chromatography. Extraction with an organic solvent is preferred.
  • Organic solvents suitable for this purpose include n-hexane, chloroform, methanol, ethanol, butanol, acetone, acetic acid, water and mixtures thereof.
  • a methanol-hexane-hexane mixed solution containing acetic acid is preferred.
  • the amount of the organic solvent used for the extraction is 0.1 to 1000 times, preferably 1 to 100 times the amount of the biological sample or a dilution thereof. Separation can be omitted when the specificity of quantification is high, such as when quantification is performed using an antibody.
  • the marker substance added to monitor the progress of oxidation and the means for quantifying oxidized or non-oxidized oxidizable substrates depend on the nature of the oxidizable substrate. If the analyte is lipids such as cholesterol esters, neutral lipids, and phospholipids, or their oxidation products, use common methods for measuring oxidized lipids or TBA-reactive substances. If it is a protein such as hemoglobin or an oxidation product thereof, a general protein assay or acid A method for measuring denatured protein can be used. In addition, HPLC, LC-EDC, TLC, mass spectrometry, ELISA, and quantification based on changes in absorbance or fluorescence intensity due to color development can be used.
  • the HPLC method or the ELISA method is preferable because it can be used for measurement of all kinds of analytes, and the identification of the analytes is possible.
  • the HP LC method equipped with a UV detector is preferable in terms of operability and cost.
  • the oxidation product when the oxidizable substrate is a lipid, the oxidation product includes a lipid peroxide which has a peroxy bond (-0-0-) in the molecule by oxidation, Lipid oxides having an oxy bond (1 O-) and lipids having a gen bond formed by their elimination. Therefore, when the oxidizable substrate is a cholesterol ester, its oxidation products include, for example, cholesterol ester hydroperoxide, cholesterol ester hydroxide, sterol oxide ester, cholesteryl ester aldehyde, and the like. It is preferable to measure the total amount of cholesterol ester hydroperoxide and cholesteryl ester hydroxide.
  • the oxidizable substrate is cholesterol ester
  • the antioxidant component in vivo is a-tocopherol
  • the oxidation reaction is initiated at AAPH, and the oxidation reaction is performed for 8 hours
  • the concentration of AAPH is preferably between 8 and 12 mM, most preferably 1 OmM.
  • diagnosis of a disease or prognosis evaluation and / or prediction of progress of a disease of a target patient can be performed based on the antioxidant ability of a biological sample evaluated by the above method.
  • Diseases of interest and Z or pathology include those for which oxidative stress is known to be an exacerbating factor, such as cataracts, diabetes, Alzheimer's, cancer, arteriosclerosis, cardiopulmonary disease, hypercholesterolemia, Chronic inflammatory diseases, ischemic diseases, etc., among which diseases involving oxidative stress in particular, such as chronic endocrine diseases such as diabetes, brain diseases such as Alzheimer, and chronic obstructive pulmonary disease (COPD) Pulmonary disease, liver disease associated with nonalcoholic fatty liver (NASH), kidney disease such as chronic renal failure, arteriosclerosis Cardiovascular diseases, Crohn's disease, chronic inflammatory diseases such as rheumatism, and cancer.
  • NASH nonalcoholic fatty liver
  • kidney disease such as chronic renal failure
  • arteriosclerosis Cardiovascular diseases arteriosclerosis Cardiovascular diseases, Cr
  • a further aspect of the present invention is to add an antioxidant test component to a biological sample containing an antioxidant component and an oxidizable substrate to initiate an oxidation reaction, and the antioxidant component is consumed by the oxidizing species.
  • a method for evaluating the antioxidant ability of an antioxidant test component which comprises continuing the oxidation reaction without exhaustion and quantifying the oxidizable substrate oxidized by the oxidation reaction.
  • This method involves placing an antioxidant test component under the mechanism of the oxidation reaction of an oxidizable substrate in a biological sample that occurs in the presence of the antioxidant component. It is intended to evaluate the antioxidant ability of the components.
  • the evaluation target is not the biological sample, but the antioxidant ability of the antioxidant test component. According to this method, it is possible to evaluate the antioxidant ability of the antioxidant test component with respect to the oxidation reaction that proceeds even in the presence of the antioxidant component in the living body.
  • a biological sample, an oxidizable substrate contained in the biological sample, an antioxidant which may be naturally contained or added to the biological sample, a means for initiating and continuing the oxidation reaction, and The quantification of oxidation products is as described above.
  • the biological sample is only one of the test materials, it is preferable that the composition and the antioxidant capacity remain unchanged.
  • a standard biological sample should be prepared in advance.
  • the biological sample is mixed with the antioxidant test component, or may be used as a control for comparison with the antioxidant test component. May be used.
  • Antioxidant Test components include synthetic or natural compounds that are expected to have antioxidant properties. Since these are compounds expected to have antioxidant properties in the future, their structures and origins cannot be specified in advance. However, the synthesized compounds include, for example, 4,6-di-tert-butyl-5-hydroxy-1,2-di-n-pentyl-2,3-dihydrobenzofuran (hereinafter referred to as B-653) Is included.
  • the molar ratio of the antioxidant test component to the antioxidant component contained in the biological sample is 0.001 to 1000: 1, preferably 0.002 to 500: 1, more preferably 0.01 to 100: 1, and still more preferably. Is 0.1 to 10: 1.
  • Example 1 Quantitative reproducibility of cholesterol ester oxidation products in plasma samples The cholesterol esters in plasma samples of normal subjects were regarded as oxidizable substrates, and the quantitative reproducibility of the oxidation products was examined.
  • Heparin blood was collected from one normal person who obtained informed consent to prepare bull plasma.
  • the pooled plasma was dispensed in 1.1 mL portions into nine test tubes and stored frozen at 180 ° C.
  • the reaction was stopped by immersing the three containers containing the respective reaction solutions in ice. Lipids in the reaction solution were extracted by adding 1 mL of a methanol solution containing 0.02% acetic acid and 5 mL of hexane to each of the 10 O ⁇ L reaction solutions. 4 mL of the hexane extract was concentrated with SpeedVac (AES1010, manufactured by ThermoSavant), and each concentrate was dissolved in 20 O ⁇ L of isopropyl alcohol.
  • SpeedVac AES1010, manufactured by ThermoSavant
  • the lipid was eluted by HPLC using a C18 reverse phase column under the following conditions. Detection was performed with 234 nm UV light.
  • UV detector (234mn, Agilent 1100 UV variable wavelength detector ⁇
  • the daily fluctuation is the percentage of the standard deviation from the daily average of samples A, B, and C measured on the same day, and the daily fluctuation is the standard deviation from the daily average for the first to third days. It is the percentage of deviation.
  • Example 2 Dependence of AAPH concentration in the presence of antioxidant components The same measurement as in Example 1 was carried out except that the concentration of AAPH in the plasma sample was varied from 0 to 48 mM. In the measurement method of the present invention, the dependency of maintaining the presence of an antioxidant component on the AAPH concentration was examined. The result is shown in figure 2. From Fig. 2, it can be seen that oxidation of CE ⁇ H and CEOH proceeds when the AAPH concentration is 5 mM or more.
  • Fig. 4 shows the results.
  • the concentrations of antioxidants shown in Fig. 4 indicate only those added from outside to the plasma sample. In reality, there is native ⁇ -tocopherol in all plasma samples. Therefore, the concentration of human tocopherol in the sample to which ⁇ -tocopherol was added from the outside is higher than the value indicated.
  • the antioxidant ability of the living body with respect to the oxidation reaction which arises in the state in which antioxidant components, such as 1 tocopherol exists can be evaluated.
  • the oxidation reaction occurring in the presence of ⁇ -tocopherol, which is an antioxidant component is considered to be important. Therefore, the present invention is useful as a clinical test method.

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Abstract

L'invention concerne un procédé d'évaluation de la capacité antioxydante d'un échantillon d'organisme consistant: (a) à prélever sur un organisme un échantillon contenant au moins un substrat à oxyder, (b) à commencer l'oxydation du substrat, (c) à poursuivre l'oxydation susmentionnée et (d) à déterminer un produit d'oxydation provenant du substrat à oxyder en mesurant le taux d'oxydation au cours de l'oxydation susmentionnée ou en réalisant une mesure après l'arrêt de l'oxydation, les étapes (b) et (c) étant exécutées en présence d'un ou de plusieurs composants antioxydants.
PCT/JP2004/003873 2003-03-20 2004-03-22 Procede d'evaluation de la capacite antioxydante d'un echantillon d'organisme Ceased WO2004083869A1 (fr)

Priority Applications (3)

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JP2005503775A JPWO2004083869A1 (ja) 2003-03-20 2004-03-22 生体試料の抗酸化能力を評価する方法
EP04722400A EP1612559A4 (fr) 2003-03-20 2004-03-22 Procede d'evaluation de la capacite antioxydante d'un echantillon biologique
US10/549,676 US20060177888A1 (en) 2003-03-20 2004-03-22 Method for evaluating antioxidation capability of organism sample

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JP2003077382 2003-03-20

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JP2006349457A (ja) * 2005-06-15 2006-12-28 Tokyo Medical & Dental Univ 非アルコール性脂肪肝の治療薬のスクリーニング方法
JP2007024871A (ja) * 2005-06-15 2007-02-01 National Institute Of Advanced Industrial & Technology 腎症関連疾患の診断方法及び診断キット
WO2012014524A1 (fr) * 2010-07-30 2012-02-02 株式会社エリナ Composition d'amélioration du métabolisme du sucre, et préparation pharmaceutique contenant ladite composition
JP2013083479A (ja) * 2011-10-06 2013-05-09 Tosoh Corp リポタンパク中のコレステロールおよびビタミンｅ類の測定方法、ならびに当該方法を利用した測定装置
JP2017219468A (ja) * 2016-06-09 2017-12-14 東ソー株式会社 リポ蛋白中ビタミンｅを用いた薬物の抗酸化効果の評価方法
WO2019235011A1 (fr) * 2018-06-06 2019-12-12 株式会社島津製作所 Procédé d'analyse et dispositif d'analyse

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US7241622B2 (en) * 2004-04-22 2007-07-10 Kemin Industries, Inc. Method for high throughput screening of antioxidants at near ambient temperatures
PT2247949T (pt) * 2008-01-25 2017-08-25 Bayer Consumer Care Ag Método de seleção de antioxidantes para utilização em composições aplicadas por via tópica

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006349457A (ja) * 2005-06-15 2006-12-28 Tokyo Medical & Dental Univ 非アルコール性脂肪肝の治療薬のスクリーニング方法
JP2007024871A (ja) * 2005-06-15 2007-02-01 National Institute Of Advanced Industrial & Technology 腎症関連疾患の診断方法及び診断キット
WO2012014524A1 (fr) * 2010-07-30 2012-02-02 株式会社エリナ Composition d'amélioration du métabolisme du sucre, et préparation pharmaceutique contenant ladite composition
KR20130112711A (ko) * 2010-07-30 2013-10-14 가부시키가이샤 에리나 당대사 개선용 조성물 및 그 조성물을 함유하는 의약 제제
US8692023B2 (en) 2010-07-30 2014-04-08 Erina Co., Inc. Sugar metabolism improving composition, and pharmaceutical preparation containing said composition
KR101708368B1 (ko) 2010-07-30 2017-02-20 가부시키가이샤 에리나 당대사 개선용 조성물 및 그 조성물을 함유하는 의약 제제
JP2013083479A (ja) * 2011-10-06 2013-05-09 Tosoh Corp リポタンパク中のコレステロールおよびビタミンｅ類の測定方法、ならびに当該方法を利用した測定装置
JP2017219468A (ja) * 2016-06-09 2017-12-14 東ソー株式会社 リポ蛋白中ビタミンｅを用いた薬物の抗酸化効果の評価方法
WO2019235011A1 (fr) * 2018-06-06 2019-12-12 株式会社島津製作所 Procédé d'analyse et dispositif d'analyse
JPWO2019235011A1 (ja) * 2018-06-06 2021-06-17 株式会社島津製作所 分析方法および分析装置
JP7107368B2 (ja) 2018-06-06 2022-07-27 株式会社島津製作所 分析方法

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